3mqm: Difference between revisions

Latest revision as of 08:59, 6 September 2023

Crystal Structure of the Bromodomain of human ASH1L

Structural highlights

3mqm is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.54Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ASH1L_HUMAN Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.

Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ An S, Yeo KJ, Jeon YH, Song JJ. Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J Biol Chem. 2011 Mar 11;286(10):8369-74. Epub 2011 Jan 14. PMID:21239497 doi:10.1074/jbc.M110.203380
↑ Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 2012 Mar 30;149(1):214-31. PMID:22464331 doi:10.1016/j.cell.2012.02.013

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OCA

[1] An S, Yeo KJ, Jeon YH, Song JJ. Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J Biol Chem. 2011 Mar 11;286(10):8369-74. Epub 2011 Jan 14. PMID:21239497 doi:10.1074/jbc.M110.203380

[2] Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 2012 Mar 30;149(1):214-31. PMID:22464331 doi:10.1016/j.cell.2012.02.013

[1]

[2]

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Bromodomain of human ASH1L==
-<StructureSection load='3mqm' size='340' side='right' caption='[[3mqm]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
+<StructureSection load='3mqm' size='340' side='right'caption='[[3mqm]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3mqm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MQM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MQM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3mqm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MQM FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASH1L, KIAA1420, KMT2H ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.54&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mqm OCA], [https://pdbe.org/3mqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mqm RCSB], [https://www.ebi.ac.uk/pdbsum/3mqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mqm ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mqm OCA], [http://pdbe.org/3mqm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mqm RCSB], [http://www.ebi.ac.uk/pdbsum/3mqm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mqm ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ASH1L_HUMAN ASH1L_HUMAN]] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).<ref>PMID:21239497</ref>
+[https://www.uniprot.org/uniprot/ASH1L_HUMAN ASH1L_HUMAN] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).<ref>PMID:21239497</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 32: @@
 __TOC__
 </StructureSection>
-[[Category: Histone-lysine N-methyltransferase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Canning, P]]
+[[Category: Canning P]]
-[[Category: Chaikuad, A]]
+[[Category: Chaikuad A]]
-[[Category: Delft, F von]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M]]
+[[Category: Felletar I]]
-[[Category: Felletar, I]]
+[[Category: Filippakopoulos P]]
-[[Category: Filippakopoulos, P]]
+[[Category: Keates T]]
-[[Category: Keates, T]]
+[[Category: Knapp S]]
-[[Category: Knapp, S]]
+[[Category: Krojer T]]
-[[Category: Krojer, T]]
+[[Category: Picaud S]]
-[[Category: Picaud, S]]
+[[Category: Vollmar M]]
-[[Category: Structural genomic]]
+[[Category: Weigelt J]]
-[[Category: Vollmar, M]]
+[[Category: Von Delft F]]
-[[Category: Weigelt, J]]
-[[Category: Absent small and homeotic disks protein 1 homolog]]
-[[Category: Ash1]]
-[[Category: Ash1l]]
-[[Category: Kiaa1420]]
-[[Category: Kmt2h]]
-[[Category: Lysine n-methyltransferase 2h]]
-[[Category: Sgc]]
-[[Category: Transferase]]

3mqm: Difference between revisions

Latest revision as of 08:59, 6 September 2023

Crystal Structure of the Bromodomain of human ASH1L

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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